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Tangential flow planar microfabricated fluid filter

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US6387290B1
US6387290B1 US09346717 US34671799A US6387290B1 US 6387290 B1 US6387290 B1 US 6387290B1 US 09346717 US09346717 US 09346717 US 34671799 A US34671799 A US 34671799A US 6387290 B1 US6387290 B1 US 6387290B1
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channel
feed
filtrate
flow
barrier
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James P. Brody
Thor D. Osborn
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University of Washington
Washington University in St Louis
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University of Washington
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by the preceding groups
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483Physical analysis of biological material
    • G01N33/487Physical analysis of biological material of liquid biological material
    • G01N33/49Blood
    • G01N33/491Blood by separating the blood components
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D39/00Filtering material for liquid or gaseous fluids
    • B01D39/14Other self-supporting filtering material ; Other filtering material
    • B01D39/16Other self-supporting filtering material ; Other filtering material of organic material, e.g. synthetic fibres
    • B01D39/1692Other shaped material, e.g. perforated or porous sheets
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D61/00Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis, ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/14Ultrafiltration; Microfiltration
    • B01D61/18Apparatus therefor
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D67/00Processes specially adapted for manufacturing semi-permeable membranes for separation processes or apparatus
    • B01D67/0039Inorganic membrane formation
    • B01D67/0053Inorganic membrane formation by inducing porosity into non porous precursor membranes
    • B01D67/0058Inorganic membrane formation by inducing porosity into non porous precursor membranes by selective elimination of components, e.g. by leaching
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D67/00Processes specially adapted for manufacturing semi-permeable membranes for separation processes or apparatus
    • B01D67/0039Inorganic membrane formation
    • B01D67/0053Inorganic membrane formation by inducing porosity into non porous precursor membranes
    • B01D67/006Inorganic membrane formation by inducing porosity into non porous precursor membranes by elimination of segments of the precursor, e.g. nucleation-track membranes, lithography or laser methods
    • B01D67/0062Inorganic membrane formation by inducing porosity into non porous precursor membranes by elimination of segments of the precursor, e.g. nucleation-track membranes, lithography or laser methods by micromachining techniques, e.g. using masking and etching steps, photolithography
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D71/00Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
    • B01D71/02Inorganic material
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502753Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D2323/00Details relating to membrane preparation
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D2323/00Details relating to membrane preparation
    • B01D2323/08Specific temperatures applied
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D2323/00Details relating to membrane preparation
    • B01D2323/12Specific ratios of components used
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/12Specific details about manufacturing devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • B01L2300/0681Filter
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0816Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0864Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0403Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406Moving fluids with specific forces or mechanical means specific forces capillary forces
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0475Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S977/00Nanotechnology
    • Y10S977/902Specified use of nanostructure
    • Y10S977/904Specified use of nanostructure for medical, immunological, body treatment, or diagnosis
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/25Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/25375Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]

Abstract

A microfilter utilizing the principles of tangential flow to prevent clogging, and sloped channel sides to overcome surface tension effects is provided which has feed inlet and exit connected by a feed flow channel; a barrier channel parallel to the feed flow channel, and a filtrate collection channel parallel to the barrier channel so that liquid can flow from the feed flow channel through the barrier channel which is too small to accommodate the particles, into the filtrate collection channel, and from then through a filtrate flow channel to a filtrate exit. Several picoliters of cell-free plasma are recovered from one drop of blood for analysis.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of application Ser. No. 08/665,218 filed Jun. 14, 1996 now U.S. Pat. No. 5,922,210, which is incorporated herein by reference to the extent not inconsistent herewith. Benefit is claimed to U.S. Provisional 60/000,281 filed on Jun. 16, 1995.

This invention was made with government support under Army research contract DAMD17-94-J-4460 awarded by the U.S. Army. The government has certain rights in the invention.

FIELD OF THE INVENTION

This invention relates generally to microfilters useful, for example, for separating plasma from whole blood. Analyzable quantities of plasma, i.e., from about 1 picoliter to a few hundred nanoliters, can be separated from one drop of whole blood within a few seconds by microfilters of this invention.

BACKGROUND OF THE INVENTION

Many blood tests must be performed on plasma without cellular matter present. In the standard laboratory protocol, pure plasma is obtained through centrifugation. In order to produce a miniaturized blood sensor, a method to separate plasma other than centrifugation is needed.

Chemical analysis of biological samples is constrained by sample size. Withdrawing a few milliliters of blood from an adult may have little effect, but repeating this procedure every hour or even withdrawing this amount once from an infant can significantly alter the health of the subject. For these reasons, a miniaturized blood analysis system would be useful. Furthermore, while many sophisticated tests that have great importance for critical care can be performed in major hospital laboratories, a substantial impact could be made on the practice of emergency medicine if some key tests could be performed on the patient at the site of injury.

Microfabricated fluid filters exist in the literature; however, these lack the advantages of the microfilter of the present invention.

Kittisland, G., and Stemme, G. (1990), “A Sub-micron Particle Filter in Silicon,” Sensors and Actuators, A21-A23:904-907; and Stemme, G. and Kittisland, G. (1988), “New fluid filter structure in silicon fabricated using a self-aligning technique,” Appl. Phys. Lett. 53:1566-1568, describe microfilters fabricated using a silicon wafer and capable of filtering out particles down to 50 nm. This filter design cannot be etched into the surface of a silicon wafer. Further, although these filters seem to a perform well for gases, surface tension causes problems when filtering liquids. Gravesen, P., et al. (1993), “Microfluidics—a review,” J. Micromech. Microeng. 3:168-182.

Wilding, P., et al. (1994), “Manipulation and Flow of Biological Fluids in Straight Channels Micromachined in Silicon,” Clin. Chem. 40:43-47 disclose microfilters useful for separating blood cells from plasma etched into silicon wafers using a photolithographic process. These filter designs do not allow tangential or crossflow of the feed material past the barrier, which may be a narrower channel or barrier posts, to clear the barrier of particles. Further, in all cases, pressure must be applied to the system to obtain analyzable quantities of plasma. Because the minimum dimension of these filters is determined by a photolithographic process, they have a limit of about 1 micron. The photolithographic process is more sensitive to defects and requires tighter constraints on manufacturing than a process that relies on etching time to define the size of the channels as is used herein.

Wilding, P., et al. U.S. Pat. No. 5,304,487 issued Apr. 19, 1994 discloses mesoscale analytical devices for fluid handling comprising flow channels and fluid handling regions micromachined into silicon wafers. Again, no microfilters having tangential flow capabilities to aid in keeping the barrier free of particles are disclosed.

Raehse, W., et al. U.S. Pat. No. 4,751,003 issued Jun. 14, 1988 discloses a microfilter using a crossflow principle having polysulfone tubes with micropore diameters of 0.3 to 0.5 microns disposed in a cylindrical configuration. Ehrfeld, W. et al. U.S. Pat. No. 4,797,211 issued Jan. 31, 1989 discloses a crossflow microfilter comprising a microporous membrane having slit-shaped cross-sections. Solomon, H., et al. U.S. Pat. No. 4,212,742 issued Jul. 15, 1980 discloses a filtration apparatus for separating blood cells from liquids utilizing crossflow principles comprising multiple layers and membrane filters.

Ehrsam, C. et al. U.S. Pat. No. 4,801,379 issued Jan. 10, 1989 discloses a microfilter made of a foil having pores set into protuberances on the foil to aid in prevention of clogging. Hillman, R. U.S. Pat. No. 4,753,776 issued Jun. 28, 1988 discloses a microfilter useful for separating plasma from red blood cells comprising glass fibers using capillary action to promote flow.

Shoji, S. and Esashi, M. (1994), “Microflow devices and systems,” J. Micromechanics and Microengineering 4:157-171, provide a general review of microvalves, micropumps, microflow sensors and integrated flow systems.

None of the foregoing references disclose or suggest the microfilter design disclosed herein which provides for tangential flow, ease and control of manufacturing, and minimization of surface tension problems.

All patents and publications referenced herein are incorporated by reference herein in their entirety.

SUMMARY OF THE INVENTION

This invention provides a microfilter useful for treating a feed liquid to separate liquid from particles contained therein comprising the following elements:

a) a feed inlet;

b) a feed exit;

c) a feed flow channel having a minimum dimension sufficient to permit flow of the particles and liquid therethrough, disposed between and in fluid communication with the feed inlet and the feed exit;

d) a filtrate collection channel parallel to the feed flow channel;

e) a barrier channel parallel to, between, and in fluid communication with the feed flow channel and the filtrate collection channel; the barrier channel having a minimum dimension sufficiently small to permit flow of the liquid but not the particles therethrough;

f) a filtrate exit in fluid communication with the filtrate collection channel;

wherein the elements are formed into the surface of a horizontal substrate; and

wherein the surface of the horizontal substrate is covered by a lid.

Preferably the microfilter also comprises a filtrate outlet channel connecting the filtrate collection channel and the filtrate exit.

Methods for making and using the microfilters of this invention are also provided.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a schematic diagram of a filter design of this invention (not to scale).

FIG. 2 is a cross section taken along line 22 of FIG. 1 showing the feed flow channel, barrier channel and filtrate collection channel of a microfilter of this invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

FIG. 1 shows a microfilter of this invention comprising a feed inlet 1 depicted as a square port, a feed exit 2 depicted as a square port, a filtrate exit 3 depicted as a square port, a feed flow channel 4 connecting the feed inlet 1 and feed exit 2, a barrier channel 5 disposed between the feed flow channel 4 and filtrate collection channel 6, and a filtrate outlet channel 7 connecting the barrier channel 5 with the filtrate exit 3.

Feed liquid containing particles enters at feed inlet 1 at the upper right and flows to feed exit 2 at the upper left. Some particle-free fluid is pushed across barrier channel 5 into filtrate collection channel 6 and from thence down to filtrate exit 3 through filtrate outlet channel 7. By controlling the pressure drop between the feed inlet 1 and the filtrate exit 3, it is possible to control how quickly and how much filtrate is drawn out. Shear forces in the feed flow channel 4 act to prevent clogging of barrier channel 5 by particles.

FIG. 2 is a cross section (not to scale) taken along line 22 of FIG. 1 showing feed flow channel 4, barrier channel 5 and filtrate collection channel 6 as well as substrate 11 and lid 10. The channels in the silicon substrate are etched using an anisotropic etchant to give characteristic V-shaped grooves. The corners between feed flow channel 4 and feed inlet 1, between feed flow channel 4 and feed exit 2, and between filtrate collection channel 6 and filtrate exit 3 are not actually as sharp as shown, resulting in an enlargement of the cross-section of the channels as they interface with the inlet and exits, which is critical to preventing surface tension lock in the absence of pressurization of the system. The barrier channel is etched in a different step from the flow channels and can be anywhere from 0.010 micron to a few microns deep. The lid is preferably Pyrex glass attached to the substrate by anodic bonding, as is known in the art. In practice, the lid may have a tendency to bow in and may tend to close off channels such as barrier channel 5 which may be less than one micron deep. To solve this problem, spacers may be designed in the barrier channel by etching the channel to leave unetched bridges across it. Preferred spacers are about 10 microns long, placed at 30 micron intervals across the width of barrier channel 5.

The term “microfilter” means a filter capable of separating fluid from particles down to 0.1 microns or less in size (average diameter). Thus the barrier channel may have a depth less than 0.1 micron, i.e., at least sufficiently small that 0.1 micron particles are unable to flow therethrough. In another embodiment, the barrier channel has a depth of about 0.01 micron so that particles down to near 0.010 micron in size are unable to flow through. The flow channels preferably have depths from about 0.1 micron up to about 300 microns, and widths preferably from about 0.1 micron to about 500 microns, although they may be wider if desired. The microfilters of this invention are designed to handle small quantities, e.g. less than about 10 microliters, and preferably about 1 microliter (less than one drop) of feed liquid and are capable of providing filtrate in analyzable quantities, such as picoliter and nanoliter amounts, e.g., between about one picoliter and about 500 nanoliters, when one microliter of feed liquid is used.

The feed liquid may be any liquid comprising particles too large to flow through the barrier channel. Preferably the feed liquid is blood, the liquid to be separated is plasma, and the particles are blood cells. Red blood cells are disk-shaped, about 2 microns thick and about 8 microns in diameter. White blood cells are irregularly shaped, averaging about 15 microns in diameter. Cell-free plasma is produced at the filtrate exit. Preferably the liquid is a polar liquid, more preferably an aqueous liquid. The microfilter may be designed for use with polar or nonpolar liquids. The surfaces of the microfilter should be treated, as is known to the art, to render them hydrophilic or hydrophobic such that they will be wetted by the type of feed liquid used.

The microfilters of this invention are capable of separating an analyzable quantity of liquid from a feed liquid containing particles which are too large to pass through the barrier channel. It is not necessary that the microfilters of this invention be capable of removing all the particles present in all the feed liquid, only that a sufficient quantity of filtrate free of larger particles be delivered from the filtrate exit of the microfilter to permit analysis thereof. The desired output of the microfilters of this invention is a quantity of liquid from which particles have been removed, rather than the particles themselves or the full amount of the feed liquid.

The feed inlet 1 may be any size and shape capable of receiving sufficient feed liquid to provide an analyzable quantity of filtrate liquid. The feed inlet may be a feed inlet port as shown in FIG. 1, etched into the horizontal substrate as depicted in FIG. 1; however, the feed inlet may be part of another connected device used for previous handling of the feed liquid, e.g., heating, separation, mixing, etc. Preferably the feed inlet is a square-shaped hollow etched completely through the silicon wafer of the preferred embodiment, about 1 mm by 1 mm, having approximately the same depth as the feed flow channel. Connections with other devices are then made from the rear of the wafer. Because of the etching process used in the preferred embodiment in which the etchant attacks the {100} planes of the silicon substrate, the feed inlet 1 of the microfilter of FIG. 1 will have sides sloping at an angle of about 55 degrees.

The feed exit 2 may similarly be of any size and shape convenient for collection of feed liquid from which some or none of the particles and some of the liquid have been removed and may be part of a connected device used for further handling or disposal of the feed liquid. The feed exit 2 may be a feed exit port as shown in FIG. 1 of the same size and shape as the feed inlet 1.

The feed flow channel 4 connecting the feed inlet 1 and the feed exit 2 should have a narrowest dimension wide enough to accommodate the particles in the feed liquid as it flows from the feed inlet 1 to the feed exit 2 past the barrier channel 5, and to provide a flow velocity under the influence of capillary action sufficient to provide a Reynolds number less than that at which inertial effects are negligible, as is more fully discussed hereinafter. In a preferred embodiment hereof, the feed flow channel 4 has a width of about 50 to about 200 microns, a depth of about 50 to about 200 microns, and is substantially V-shaped. However, the feed flow channel can be as wide and deep as desired.

A filtrate collection channel 6 runs generally parallel to the feed flow channel 4. The filtrate collection channel 6 preferably is as long as possible to maximize the throughput, and together with filtrate outlet channel 7 should have a volume large enough to collect an analyzable quantity of filtrate. Preferably, the filtrate collection channel 6 is a few millimeters long, e.g., about 3-5 mm, and of the same depth, width and shape as the feed flow channel 4, although it may be a wide pool or reservoir. It may be any shape capable of holding the collected filtrate.

The feed flow channel 4 and the filtrate collection channel 6 are separated from each other by a barrier channel 5 having a smaller minimum dimension than the feed flow channel 4 such that liquid may pass from the feed flow channel 4 and flow into the barrier channel 5 and from there into the filtrate collection channel 6, but the particles desired to be separated from the feed liquid remain in the feed flow channel 4. The barrier channel 5 is of a length sufficient to allow flow of sufficient liquid for analysis from the feed flow channel 4 even in the absence of system pressurization. Preferably, the barrier channel is the same length as the filtrate collection channel 6. In a preferred embodiment, the barrier channel 5 is about the same width as the feed flow channel 4, although it may be wider to provide greater ease of fabrication consistent with facilitating throughput. The barrier channel 5 may have a depth of less than about 0.1 micron down to about 0.010 micron, and preferably has a depth about 0.5 micron or less. This will preclude blood cells having a maximum dimension of about 8 microns or larger from passing through the barrier channel. The barrier channel 5 is generally too shallow to have the substantially V-shaped profile of the flow channels.

Where no external pressure is present, the surface tension of the fluid alone should be enough to provide initial wetting of the device. This initial wetting provides some flow across the barrier channel 5 and hence some particle-free fluid in filtrate collection channel 6. To prevent surface tension lock, it is important to provide for gradual changes in the curvature of the fluid/air interface. Where there is an abrupt change in the diameter of a channel (from narrow to wide), fluid will not flow through by means of capillary action alone; however, if the diameter change is gradual, capillary action will cause sufficient fluid flow through the filter to produce analyzable quantities of filtrate. The etching process of this invention provides gradual widening of feed flow channel 4 as it connects with the feed inlet 1 so as to prevent surface tension lock, and provides gradual widening of filtrate outlet channel 7 as it connects with filtrate exit 3 to prevent surface tension lock.

The arrangement of the barrier channel 5 with respect to the feed flow channel 4 provides a tangential flow of the feed liquid past the barrier channel which tends to avoid clogging of the barrier channel, as the particles are swept into the flow of the feed material toward the feed exit.

The filtrate collection channel 6 is preferably the same length as the barrier channel 5 and is in fluid communication with it along its entire length to allow maximum flow of filtrate liquid toward the filtrate exit 3.

The filtrate exit 3 has a volume sufficient to accommodate an analyzable quantity of filtrate as discussed above. Again, the filtrate exit 3 can be part of a connected device such as a device for performing a separation, heating, mixing, or analytical step, for example as described in Wilding et al., U.S. Pat. No. 5,304,487. Preferably, the filtrate exit 3 is a filtrate exit port as shown in FIG. 1 of the same size and shape as feed inlet 1.

The filtrate exit 3 is in fluid communication with the filtrate outlet channel 7 preferably by means allowing free flow of filtrate into the filtrate exit 3 in the absence of pressurization of the system. In other words, the surface tension of the filtrate flowing into the filtrate exit 3 must be capable of being overcome by the pressure exerted by capillary action alone. The filtrate may be removed from filtrate collection channel 6 by any means known to the art. The filtrate collection channel 6 may comprise the filtrate exit point. Preferably, the filtrate exit 3 is connected to the filtrate collection channel 6 by a filtrate outlet channel 7 having a conformation which permits free flow of the filtrate therethrough against the force exerted by surface tension, e.g., gradual changes in curvature rather than sharp edges. As more fully discussed hereinafter, the etching process used to form the substantially V-shaped channels of this invention results in a gradual widening of the channels sufficient to overcome the force of surface tension as discussed above.

The microfilter of this invention is capable of being formed on a substrate by microfabrication techniques known to the art, 30 preferably by etching the flat surface of a silicon wafer and cutting to form a device about 1 cm by about 1 cm, and about 300 microns thick. Preferably these are {100} wafers (n-type or p-type) having at least about 100 to about 500 nm of silicon dioxide grown on the surface.

The length of the channels is between about 1 micron and several millimeters, and the depth anywhere from about 0.010 micron to the thickness of the wafer, e.g., about 300 microns. The width may be about 0.1 micron to about 500 microns.

The microfilter of this invention is completed by the addition of a lid placed over the surface of the substrate, touching the raised portions, and providing a top surface for enclosing the channels and ports. Preferably this lid is transparent, and more preferably is glass bonded to the surface of the substrate.

Means for applying pressure to the flow of the feed liquid through the device may also be provided. Such means may be provided at the feed inlet, the filtrate exit (as vacuum), or both. Means for applying such pressure are known to the art, for example as described in Shoji, S. and Esashi, M. (1994), “Microflow devices and systems,” J. Micromechanics and Microengineering, 4:157-171, and include the use of a column of water or other means of applying water pressure, electroendoosmotic forces, optical forces, gravitational forces, and surface tension forces. Pressures from about 10−6 psi to about 10 psi may be used, depending on the requirements of the system. Preferably about 10−3 psi is used when pressure is required.

When it is desired to reuse the microfilters of this invention, means for providing backflow of fluid across the barrier channel 5 to clear the particles therefrom may be provided. Pressurizing the filtrate exit 3 to about half the pressure being put on the feed inlet 1 generally provides sufficient backflow to clear the device.

In a preferred embodiment of this invention, microfilters of this invention have hydrophilic surfaces to facilitate flow of liquid therein and allow operation of the device without the necessity for pressurization. The substrate may be treated by means known to the art following fabrication of the channels, to render it hydrophilic. The lid is also preferably treated to render it hydrophilic.

The preferred process for making microfilters of this invention comprises:

a) providing a {100} silicon wafer;

b) etching a feed flow channel and a filtrate collection channel into the silicon wafer of step a) with an etchant capable of attacking the {100} planes of said silicon wafer to form substantially V-shaped channels; and

c) etching a barrier channel into said silicon wafer.

A {100} silicon wafer is one in which the major surfaces are substantially {100} planes, although sometimes the orientation in these commercially available wafers is not precise. The etching is preferably done using EPW F-etch as described in Reisman, A., et al. (1979), J. Electrochem. Soc. 126:1406-1415, or another etchant capable of forming substantially V-shaped channels such as potassium hydroxide in a mixture of water and isopropyl alcohol. Preferably the etching is done in three stages, timed to provide the required depth for the channels and ports. In the embodiment of FIG. 1, the inlet and exit ports are preferably etched in a first step, flow channels are preferably etched in a second step, and the barrier channel, which is the shallowest, is preferably etched in a third step. As is understood by those skilled in the art, the previously-etched structures are deepened during subsequent etching steps.

A lid, preferably a glass sheet, is then bonded to the etched substrate to complete the enclosure of the ports and channels. In a preferred embodiment, the substrate and lid are first treated to render them hydrophilic.

In use, a liquid, preferably about one microliter of blood, is injected into the feed inlet 1. The liquid moves through the filter by capillary action and several picoliters of filtrate collect at the filtrate exit 3 for analysis.

Means for injecting feed liquid into the device are provided, as when the microfilter of this invention is used as part of an analytical system. Such means include standard syringes and tubes. Means for removing fluid from the filtrate exit 3 may also be provided, including receptacles for the fluid, inducing flow by capillary action, pressure, gravity, and other means known to the art as described above. Such receptacles may be part of an analytical or other device for further processing the filtrate.

Analysis of the filtrate may be by optical means known to the art such as absorption spectroscopy or fluorescence, by chemical or immunological means, or other means known to the art to detect the presence of an analyte such as a virus, DNA sequence, antigen, microorganism or other factor.

The manufacturing process of this invention minimizes the number of mask steps and wafer/wafer or wafer/glass bonding steps. In manufacturing the microfilters of this invention, size scaling is also considered. Fluid dynamic behavior is directly related to the Reynolds number of the flow. In microdevices, if the velocity decreases as the channel length (where the device is assumed to work in a fixed time at all scales), then the Reynolds number varies in proportion to the square of the length. As devices are miniaturized, the Reynolds number is inevitably reduced.

The Reynolds number is the ratio of inertial forces to viscous forces. As the Reynolds number is reduced, flow patterns depend more on viscous effects and less on inertial effects. Below a certain Reynolds number, e.g. 0.1 (based on lumen size for a system of channels with bends and lumen size changes), inertial effects can essentially be ignored. The microfluidic devices of this invention do not require inertial effects to perform their tasks, and therefore have no inherent limit on their miniaturization due to Reynolds number effects. Applicants' filter designs, while significantly different from previous reported designs, operate in this range.

The devices of the preferred embodiment of this invention provide a few hundred picoliters of plasma within a few seconds. They also may be reused. Clogging is minimized and reversible. The sizes and velocities (100 μm wide and 100 μm/s) indicate a Reynolds number (Re=plv/η) of about 10−2 so that the fluid is in a regime where viscosity dominates over inertia.

The magnitude of the pressure drop needed to obtain an average velocity, v, of a fluid with absolute viscosity, η, and density, p, through a circular channel (length, 1, diameter, d) can be calculated from Poiseuille's Law (Batchelor, G. K., An Introduction to Fluid Dynamics, Cambridge Univ. Press 1967), P 1 = 32 η v d 2

Using v=100 μm/sec and d=100 μm, we get a pressure drop equivalent to about 0.3 mm of H2O per cm of channel length. Since Poiseuille's equation is only strictly valid for circular flow channels and the channels of this invention are substantially V-shaped grooves, it can be considered only as an approximate relation between the variables represented.

When a liquid is introduced into a device there is at first an effective pressure, Peff=Po+Pst, equal to the sum of the applied pressure, Po, and a pressure due to the surface tension, P st = ϒcosΘ r .

Pst is a function of the surface tension of the fluid, γ, the contact angle of the fluid with the surface, Θ, and the radius of curvature of the fluid surface, r.

For hydrophilic surfaces, cos Θ is close to 1, and for small channels no applied pressure is needed to wet the device. This is referred to as “wetting by capillary action.” However, once the device is completely wet, one has to worry about the surface tension at the exit area. In the device described in the example hereof, the radius of curvature of the fluid in the exit area was several millimeters, so that the pressure due to the surface tension was negligible.

With a channel width of 100 μm, Pst is about 1 cm of H2O, so surface tension on the exit channel is significant. However, using an etchant such as EPW F-Etch as described below, which attacks the {100} planes of silicon, means that the corners as etched are not as sharp as shown in FIG. 2. This results in a gradual widening of the channel to about 1 mm which reduces the effect of the surface tension.

This effect also occurs in the barrier region. Using an etchant that gives a vertical (90°) profile, instead of the 55° characteristic of the {100} planes of silicon, would require a pressure as large as one atmosphere to overcome the surface tension in a 0.1 μm gap.

Since this filter design is self-priming, it can be operated in two modes. In “one-shot mode,” a drop (one μl) of blood contacts the entrance port. The blood is drawn down the channel and plasma is drawn through the filter without any applied pressure. This provides several nanoliters of plasma within a few seconds. Once fluid fills the device, flow stops. If no way is provided to flush this sample out of the device, it would have only one use.

The second mode, continuous flow mode, requires an applied pressure head. The relative pressure between the feed inlet, feed exit, and filtrate exit can be controlled to provide a continuous stream of filtrate or to induce some reverse flow through the filter which is useful for removing particles stuck on or near the barrier channel.

EXAMPLE

A three mask level process was used to fabricate a microfilter of this invention on a silicon wafer. The first level defined connection ports, which were etched completely through the wafer to the rear side of the silicon. The second level defined the fluid transport channels, and the third level defined the maximum size of particles which could flow through the filter.

Four inch chrome masks were made to these specifications by Photo Sciences, Inc. (Torrance, Calif.) and 3″ wafers ({100}, n-type) with 500 nm of SiO2 grown on them were used.

Wafers were cleaned in a Piranha bath (H2SO4 and H2O2) (2:1) before processing. A primer (HMDS spun on at 3000 rpm) was used to enhance photoresist adhesion. About one μm of AZ-1370-SF (Hoechst) photoresist was deposited by spin coating (3000 rpm), and this was followed by a soft bake (30 min at 90° C.).

A contact aligner was used to align and expose wafers. Exposure time was varied to yield best results. No post-exposure bake was done. Wafers were developed in AZ-351 (diluted 4:1) (Hoechst) for one minute and rinsed in DI water. Blue tack tape (Semiconductor Equipment Corporation, Moorpark, Calif.) was applied to the backsides of the wafers to protect the oxide from the oxide etch.

The wafers were immersed in a buffered oxide etch (BOE, 10:1 HF (49%) and NH4F (10%)) for eleven minutes to completely etch away the unprotected oxide. The blue tack tape was removed by hand, and the photoresist was removed in an acetone rinse.

Silicon etching was done in a mixture of ethylene-diamine, pyro-catechol, and water (EPW F-etch as described in Reisman, A., et al. (1979) J. Electrochem. Soc. 126:1406-1415) set up in a reflux boiling flask. This etch attacks the {100} planes of silicon at a rate of about 100 μm an hour. Fluid attachment ports were etched in the first step for about three hours. Photoresist was again applied, and the mask containing flow channels between fluid ports and the barrier region was exposed. The wafers were developed and etched in this second step for about one hour. Photoresist was applied once more and the mask containing the barrier region was exposed. The wafers were developed and etched in the final step for about one minute.

After final processing, the wafers were once again cleaned in a Piranha bath and rinsed in DI water. They were then diced into individual devices about 1 cm by 1 cm.

Anodic bonding according to Wallis, G. and Pomerantz, D. I (1969) J. Appl. Physics 40:3946-3949, was used to attach Pyrex glass to the silicon devices. One inch square pieces of Pyrex glass (100 μm thickness) from Esco Products Inc. (Oak Ridge, N.J.) were used. First, the silicon and Pyrex glass were immersed in a solution of H2O2, NH4OH, and H2O (1:4:6) heated to 50° C. This process removes any organic matter on the surfaces and also makes the surfaces hydrophilic. After 20 minutes in this solution, the silicon and Pyrex were rinsed with DI water and dried. Anodic bonding was done at 400° C. with 400 V applied between the glass and the silicon.

Testing was done by flowing dilute suspensions of fluorescent microspheres through the device. One drop of 16 μm diameter fluorescing microspheres (1% solids, from Duke Scientific, Palo Alto, Calif.) was added to 5 ml of DI water. A similar mixture of 2.6 μm diameter spheres was also prepared. The 16 μm spheres fluoresce in the green and the 2.6 μm diameter spheres fluoresce in the red, making them easily discernible by eye.

This mixture was introduced into the device, and observations were made using a Zeiss ICM-405 inverted microscope. Fluorescence of the spheres was observed using a silicon intensified target camera (SIT-66x, from Dage-MTI) and observations were recorded on video tape. Some images were also digitized using a frame grabber (Data Translation) and NIH Image software.

The pressures at the inlet port and at the exit port of the filtered liquid were controlled by filling a tube to the appropriate height with liquid. The pressures at the exit port of the unfiltered feed liquid was held constant to within a few mm of H2O.

The experiment proceeded by first inserting a mixture of fluid and particles at the inlet port. Once this wet the entire device (one-shot mode), some particle build-up on the edge of the barrier channel was observed. Typically, some 16 μm spheres would build up along the barrier channel, but not to any significant depth.

The solution containing 2.6 μm spheres was then added to the inlet. These spheres freely flowed through the feed flow channel and some crossed the barrier channel.

The filter exit port was then pressurized to about half the pressure being put on the feed inlet. This resulted in a backflow across the barrier, quickly forcing the 16 μm spheres back into the flowstream where they were carried to the feed exit port.

The fluorescent spheres with a 16 micron diameter were immediately visible in the inlet port, as well as a few flowing along the feed flow channel and some pressed against the barrier channel. None passed through the barrier channel. After the introduction of 2.6 μm spheres, these smaller spheres were easily seen. Most flowed along the feed flow channel but some easily passed by the barrier which trapped the 16 μm spheres.

The preferred embodiments described above are illustrative rather than limiting of the invention. As will be readily understood by those skilled in the art, various materials, processes and parameters can be varied to achieve the objectives of this invention to provide a microfilter capable of providing analyzable quantities of particle-free liquid, and utilizing the principles of tangential flow past the barrier channel to reduce clogging, and sloped channel walls to overcome the effects of surface tension. The invention is limited only by the scope of the claims appended hereto.

Claims (24)

What is claimed is:
1. A method for making a microfilter useful for treating a feed liquid to separate liquid from particles contained therein, said method comprising:
a) providing a {100} silicon wafer;
b) etching a feed flow channel and a filtrate collection channel into the silicon wafer of step a) with an etchant capable of attacking the {100} planes of said silicon wafer to form substantially V-shaped channels; and
c) etching a barrier channel in said wafer.
2. The method of claim 1 wherein steps a), b) and c) are performed sequentially using the same etchant.
3. The method of claim 1 wherein following the etching steps, a glass lid is bonded to the etched surface of the silicon wafer.
4. The method of claim 1 wherein the etchant used is an anisotropic etchant providing a gradual widening of the channels at the inlet and exits such that flow therethrough by means of capillary action alone is facilitated.
5. A microfilter useful for treating a feed liquid to separate liquid from particles contained therein comprising the following elements formed into the surface of a horizontal substrate:
a) a feed inlet;
b) a feed exit;
c) a microfluidic feed flow channel having a minimum dimension sufficient to permit flow of the particles and liquid therethrough, disposed between and in fluid communication with the feed inlet and the feed exit;
d) a microfluidic filtrate collection channel parallel to the feed flow channel;
e) a single barrier channel parallel to, between, and in fluid communication with the feed flow channel and the filtrate collection channel; the barrier channel having a depth sufficiently small to permit flow of the liquid therethrough but not the particles; and
f) a filtrate exit in fluid communication with the filtrate collection channel.
6. The microfilter of claim 5 also comprising a filtrate outlet channel connecting the filtrate collection channel and the filtrate exit.
7. The microfilter of claim 5 also comprising means for applying pressure to the flow of the feed liquid through the microfilter.
8. The microfilter of claim 5 having hydrophilic surfaces whereby the liquid flows through the microfilter from the feed inlet to the filtrate exit without the application of pressure.
9. The microfilter of claim 5 adapted for the separation of plasma from whole blood.
10. The microfilter of claim 5 wherein the feed flow channel and the filtrate collection channel are substantially V-shaped.
11. The microfilter of claim 6 wherein the feed flow channel, the filtrate collection channel and the filtrate outlet channel are substantially V-shaped.
12. The microfilter of claim 5 wherein the feed flow channel and the filtrate collection channel are approximately 100 microns wide.
13. The microfilter of claim 6 wherein the barrier channel has a depth of less than about 0.1 micron.
14. The microfilter of claim 5 wherein the substrate is a silicon wafer.
15. The microfilter of claim 14 wherein the channels are etched by an anisotropic etchant to provide gradual widening at the inlet and exits whereby flow therethrough by means of capillary action alone is facilitated.
16. The microfilter of claim 5 comprising a lid which comprises a glass sheet.
17. The microfilter of claim 5 adapted to separate an analyzable quantity of plasma from one microliter of blood.
18. An analytical system comprising the microfilter of claim 5 and also comprising injection means for introducing the feed liquid into the feed inlet.
19. The microfilter of claim 5 comprising means in fluid communication with the filtrate exit for detecting the presence of an analyte in the filtrate.
20. The microfilter of claim 5 wherein the width of the barrier channel is greater than or about equal to the width of the feed flow channel.
21. The microfilter of claim 20 wherein the width of the barrier channel is about equal to the width of the feed flow channel.
22. A method for recovering a quantity of liquid separated from particles from a feed liquid containing said particles comprising introducing the feed liquid into the feed inlet of the microfilter of claim 5 and withdrawing separated liquid from the filtrate exit.
23. The method of claim 22 wherein the feed liquid is blood, the particles are blood cells, and the separated liquid is plasma.
24. The method of claim 23 wherein pressure is applied to the microfilter following withdrawal of separated liquid from the filtrate exit to clear the barrier channel of particles.
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Cited By (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020185431A1 (en) * 2001-06-07 2002-12-12 Nanostream, Inc. Microfluidic filter
US20030159999A1 (en) * 2002-02-04 2003-08-28 John Oakey Laminar Flow-Based Separations of Colloidal and Cellular Particles
US20040129678A1 (en) * 2002-09-07 2004-07-08 Timothy Crowley Integrated apparatus and methods for treating liquids
US20040195099A1 (en) * 2003-04-04 2004-10-07 Jacobson Stephen C. Sample filtration, concentration and separation on microfluidic devices
US20040256318A1 (en) * 2001-10-26 2004-12-23 Kazuhiro Iida Separating device, analysis system separation method and method of manufacture of separating device
WO2004113877A1 (en) * 2003-06-13 2004-12-29 The General Hospital Corporation Microfluidic systems for size based removal of red blood cells and platelets from blood
US20050129582A1 (en) * 2003-06-06 2005-06-16 Micronics, Inc. System and method for heating, cooling and heat cycling on microfluidic device
US6925392B2 (en) 2002-08-21 2005-08-02 Shell Oil Company Method for measuring fluid chemistry in drilling and production operations
WO2005095954A1 (en) * 2004-03-31 2005-10-13 All Medicus Co., Ltd. A filter for separating blood-corpuscles and plasma from blood, and blood analysis system using this filter
US20050266433A1 (en) * 2004-03-03 2005-12-01 Ravi Kapur Magnetic device for isolation of cells and biomolecules in a microfluidic environment
US20060134599A1 (en) * 2002-09-27 2006-06-22 Mehmet Toner Microfluidic device for cell separation and uses thereof
WO2006079007A2 (en) * 2005-01-21 2006-07-27 President And Fellows Of Harvard College Microconcentrator/microfilter
US20060171846A1 (en) * 2005-01-10 2006-08-03 Marr David W M Microfluidic systems incorporating integrated optical waveguides
WO2006093845A2 (en) * 2005-02-28 2006-09-08 Careside Medical Llc A micro-fluidic fluid separation device and method
US20070059718A1 (en) * 2005-09-15 2007-03-15 Mehmet Toner Systems and methods for enrichment of analytes
US20070059683A1 (en) * 2005-09-15 2007-03-15 Tom Barber Veterinary diagnostic system
US20070289917A1 (en) * 2006-06-15 2007-12-20 Mylin John M Separation system and method of operating
US20080007838A1 (en) * 2006-07-07 2008-01-10 Omnitech Partners, Inc. Field-of-view indicator, and optical system and associated method employing the same
US20090026387A1 (en) * 2007-07-03 2009-01-29 Colorado School Of Mines Optical-based cell deformability
US20090062828A1 (en) * 2007-09-04 2009-03-05 Colorado School Of Mines Magnetic field-based colloidal atherectomy
US20090081771A1 (en) * 2003-06-06 2009-03-26 Micronics, Inc. System and method for heating, cooling and heat cycling on microfluidic device
US20090110010A1 (en) * 2007-09-26 2009-04-30 Colorado School Of Mines Fiber-focused diode-bar optical trapping for microfluidic manipulation
US20090148847A1 (en) * 2006-03-15 2009-06-11 Micronics, Inc. Rapid magnetic flow assays
US20090325276A1 (en) * 2006-09-27 2009-12-31 Micronics, Inc. Integrated microfluidic assay devices and methods
US20100021910A1 (en) * 2008-07-18 2010-01-28 Canon U.S. Life Sciences, Inc. Methods and Systems for Microfluidic DNA Sample Preparation
US20100230334A1 (en) * 2009-03-12 2010-09-16 Samsung Electronics Co., Ltd. Filter unit for separating target material and microfluidic device including the filter unit
USRE41762E1 (en) 2001-02-14 2010-09-28 Stc.Unm Nanostructured separation and analysis devices for biological membranes
US20110014605A1 (en) * 2009-07-17 2011-01-20 Canon U.S. Life Sciences, Inc. Methods and systems for dna isolation on a microfluidic device
US8021614B2 (en) 2005-04-05 2011-09-20 The General Hospital Corporation Devices and methods for enrichment and alteration of cells and other particles
WO2012094170A2 (en) * 2011-01-03 2012-07-12 The Regents Of The University Of California Methods and microfluidic devices for concentrating and transporting particles
US20130264295A1 (en) * 2012-04-05 2013-10-10 Samsung Electronics Co., Ltd. Filter for capturing target material
WO2014138715A1 (en) * 2013-03-08 2014-09-12 Duke University Devices, systems, and methods for acoustically -enhanced magnetophoresis
US8921102B2 (en) 2005-07-29 2014-12-30 Gpb Scientific, Llc Devices and methods for enrichment and alteration of circulating tumor cells and other particles
US9075042B2 (en) 2012-05-15 2015-07-07 Wellstat Diagnostics, Llc Diagnostic systems and cartridges
US9132398B2 (en) 2007-10-12 2015-09-15 Rheonix, Inc. Integrated microfluidic device and methods
US9213043B2 (en) 2012-05-15 2015-12-15 Wellstat Diagnostics, Llc Clinical diagnostic system including instrument and cartridge
US9222623B2 (en) 2013-03-15 2015-12-29 Genmark Diagnostics, Inc. Devices and methods for manipulating deformable fluid vessels
US9487812B2 (en) 2012-02-17 2016-11-08 Colorado School Of Mines Optical alignment deformation spectroscopy
US9498778B2 (en) 2014-11-11 2016-11-22 Genmark Diagnostics, Inc. Instrument for processing cartridge for performing assays in a closed sample preparation and reaction system
US9598722B2 (en) 2014-11-11 2017-03-21 Genmark Diagnostics, Inc. Cartridge for performing assays in a closed sample preparation and reaction system
US9625465B2 (en) 2012-05-15 2017-04-18 Defined Diagnostics, Llc Clinical diagnostic systems

Families Citing this family (112)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6454945B1 (en) * 1995-06-16 2002-09-24 University Of Washington Microfabricated devices and methods
US6541213B1 (en) * 1996-03-29 2003-04-01 University Of Washington Microscale diffusion immunoassay
US20030211507A1 (en) * 1996-03-29 2003-11-13 Anson Hatch Microscale diffusion immunoassay in hydrogels
JP4368423B2 (en) * 1996-09-25 2009-11-18 バクスター・インターナショナル・インコーポレイテッド A system for filtering medical fluid and biological fluid
US7670429B2 (en) * 2001-04-05 2010-03-02 The California Institute Of Technology High throughput screening of crystallization of materials
US6312591B1 (en) 1997-09-10 2001-11-06 Sartorius Ag Filtration cell for tangential flow filtration and filtration system making use of such cell
US6036659A (en) 1998-10-09 2000-03-14 Flexsite Diagnostics, Inc. Collection device for biological samples and methods of use
US20020164812A1 (en) * 1999-04-06 2002-11-07 Uab Research Foundation Method for screening crystallization conditions in solution crystal growth
US7214540B2 (en) * 1999-04-06 2007-05-08 Uab Research Foundation Method for screening crystallization conditions in solution crystal growth
DE60034033T2 (en) * 1999-04-06 2007-12-06 University of Alabama, Birmingham Research Foundation, Birmingham A device for screening of crystallizing conditions for growing crystals in solutions
US7247490B2 (en) * 1999-04-06 2007-07-24 Uab Research Foundation Method for screening crystallization conditions in solution crystal growth
US20070026528A1 (en) * 2002-05-30 2007-02-01 Delucas Lawrence J Method for screening crystallization conditions in solution crystal growth
JP2003501639A (en) * 1999-06-03 2003-01-14 ユニバーシティ オブ ワシントン Microfluidic device for the transverse electrophoresis and isoelectric focusing
CA2360194C (en) * 2000-10-25 2008-10-07 Micronix, Inc. A solid state microcuvette using dry films
CN101362058B (en) 1999-12-08 2011-10-12 巴克斯特国际公司 Microporous filter membrane, method of making microporous filter membrane and separator employing microporous filter membranes
US20030168396A1 (en) * 1999-12-08 2003-09-11 Jacobson James D. Monolithic filter body and fabrication technique
US6982058B2 (en) * 1999-12-08 2006-01-03 Baxter International, Inc. Method for fabricating three dimensional structures
US6408884B1 (en) 1999-12-15 2002-06-25 University Of Washington Magnetically actuated fluid handling devices for microfluidic applications
JP4733331B2 (en) 2000-03-14 2011-07-27 マイクロニックス、インコーポレーテッド Device for micro-fluid analysis
WO2001075415A3 (en) * 2000-03-31 2002-02-28 Micronics Inc Protein crystallization in microfluidic structures
US7630075B2 (en) 2004-09-27 2009-12-08 Honeywell International Inc. Circular polarization illumination based analyzer system
US20060263888A1 (en) * 2000-06-02 2006-11-23 Honeywell International Inc. Differential white blood count on a disposable card
JP5431732B2 (en) 2005-12-29 2014-03-05 ハネウェル・インターナショナル・インコーポレーテッド Assay implementation in a microfluidic format
US7016022B2 (en) * 2000-08-02 2006-03-21 Honeywell International Inc. Dual use detectors for flow cytometry
US7630063B2 (en) * 2000-08-02 2009-12-08 Honeywell International Inc. Miniaturized cytometer for detecting multiple species in a sample
US7978329B2 (en) * 2000-08-02 2011-07-12 Honeywell International Inc. Portable scattering and fluorescence cytometer
US7262838B2 (en) * 2001-06-29 2007-08-28 Honeywell International Inc. Optical detection system for flow cytometry
US6382228B1 (en) 2000-08-02 2002-05-07 Honeywell International Inc. Fluid driving system for flow cytometry
US7471394B2 (en) * 2000-08-02 2008-12-30 Honeywell International Inc. Optical detection system with polarizing beamsplitter
US7277166B2 (en) * 2000-08-02 2007-10-02 Honeywell International Inc. Cytometer analysis cartridge optical configuration
US7283223B2 (en) * 2002-08-21 2007-10-16 Honeywell International Inc. Cytometer having telecentric optics
US7215425B2 (en) * 2000-08-02 2007-05-08 Honeywell International Inc. Optical alignment for flow cytometry
US6597438B1 (en) 2000-08-02 2003-07-22 Honeywell International Inc. Portable flow cytometry
US7061595B2 (en) * 2000-08-02 2006-06-13 Honeywell International Inc. Miniaturized flow controller with closed loop regulation
US6970245B2 (en) * 2000-08-02 2005-11-29 Honeywell International Inc. Optical alignment detection system
US6549275B1 (en) 2000-08-02 2003-04-15 Honeywell International Inc. Optical detection system for flow cytometry
US7011791B2 (en) 2000-09-18 2006-03-14 University Of Washington Microfluidic devices for rotational manipulation of the fluidic interface between multiple flow streams
US6881198B2 (en) * 2001-01-09 2005-04-19 J. David Brown Glaucoma treatment device and method
US20030040119A1 (en) * 2001-04-11 2003-02-27 The Regents Of The University Of Michigan Separation devices and methods for separating particles
US6700130B2 (en) 2001-06-29 2004-03-02 Honeywell International Inc. Optical detection system for flow cytometry
US6825127B2 (en) 2001-07-24 2004-11-30 Zarlink Semiconductor Inc. Micro-fluidic devices
US7250305B2 (en) * 2001-07-30 2007-07-31 Uab Research Foundation Use of dye to distinguish salt and protein crystals under microcrystallization conditions
DE10150549A1 (en) * 2001-10-12 2003-04-17 Roche Diagnostics Gmbh Separation module, useful for the separation of corpuscles from blood, comprises two channels from a junction with a faster flow in one channel taking most of the particles, and a slower flow with few particles through the other channel
US7473361B2 (en) * 2001-11-30 2009-01-06 Cornell Research Foundation Diffusion-based molecular separation in structured microfluidic devices
CA2468674A1 (en) * 2001-12-05 2003-06-12 University Of Washington Microfluidic device and surface decoration process for solid phase affinity binding assays
US6637257B2 (en) * 2002-01-02 2003-10-28 Integrated Sensing Systems Micromachined fluid analysis device and method
US6814859B2 (en) * 2002-02-13 2004-11-09 Nanostream, Inc. Frit material and bonding method for microfluidic separation devices
US7560267B2 (en) * 2002-03-18 2009-07-14 City University Of Hong Kong Apparatus and methods for on-chip monitoring of cellular reactions
DE10220296A1 (en) * 2002-05-07 2003-11-20 Roche Diagnostics Gmbh Device for sampling liquid samples
WO2004000444A1 (en) * 2002-06-19 2003-12-31 Northwest Biotherapeutics, Inc. Tangential flow filtration devices and methods for leukocyte enrichment
WO2004005898A1 (en) * 2002-07-10 2004-01-15 Uab Research Foundation Method for distinguishing between biomolecule and non-biomolecule crystals
US7000330B2 (en) * 2002-08-21 2006-02-21 Honeywell International Inc. Method and apparatus for receiving a removable media member
US7094345B2 (en) * 2002-09-09 2006-08-22 Cytonome, Inc. Implementation of microfluidic components, including molecular fractionation devices, in a microfluidic system
US7455770B2 (en) * 2002-09-09 2008-11-25 Cytonome, Inc. Implementation of microfluidic components in a microfluidic system
US6878271B2 (en) * 2002-09-09 2005-04-12 Cytonome, Inc. Implementation of microfluidic components in a microfluidic system
DE10252223A1 (en) * 2002-11-11 2004-05-27 Roche Diagnostics Gmbh Device for separating and output of plasma
US20040179972A1 (en) * 2003-03-14 2004-09-16 Nanostream, Inc. Systems and methods for detecting manufacturing defects in microfluidic devices
DE10313201A1 (en) * 2003-03-21 2004-10-07 Steag Microparts Gmbh contains Microstructured microfluidic separation device and method for separating liquid components from a liquid, the particles
DE102004007567A1 (en) * 2004-02-17 2005-09-01 Boehringer Ingelheim Microparts Gmbh Microstructured platform and method for handling a liquid
US7226540B2 (en) * 2004-02-24 2007-06-05 Becton, Dickinson And Company MEMS filter module
US20050194303A1 (en) * 2004-03-02 2005-09-08 Sniegowski Jeffry J. MEMS flow module with filtration and pressure regulation capabilities
US7641856B2 (en) * 2004-05-14 2010-01-05 Honeywell International Inc. Portable sample analyzer with removable cartridge
EP3121601A1 (en) * 2005-12-22 2017-01-25 Honeywell International Inc. Portable sample analyzer system
JP5175213B2 (en) 2005-12-22 2013-04-03 ハネウェル・インターナショナル・インコーポレーテッド Portable sample analysis system
WO2007075922A3 (en) 2005-12-22 2007-09-27 Ron L Bardell Portable sample analyzer cartridge
US8071051B2 (en) * 2004-05-14 2011-12-06 Honeywell International Inc. Portable sample analyzer cartridge
US7242474B2 (en) * 2004-07-27 2007-07-10 Cox James A Cytometer having fluid core stream position control
US20060118479A1 (en) * 2004-08-24 2006-06-08 Shevkoplyas Sergey S Particle separating devices, systems, and methods
US7612871B2 (en) * 2004-09-01 2009-11-03 Honeywell International Inc Frequency-multiplexed detection of multiple wavelength light for flow cytometry
US8329118B2 (en) * 2004-09-02 2012-12-11 Honeywell International Inc. Method and apparatus for determining one or more operating parameters for a microfluidic circuit
US7550267B2 (en) * 2004-09-23 2009-06-23 University Of Washington Microscale diffusion immunoassay utilizing multivalent reactants
US7130046B2 (en) * 2004-09-27 2006-10-31 Honeywell International Inc. Data frame selection for cytometer analysis
WO2006060783A3 (en) 2004-12-03 2006-09-14 Cytonome Inc Unitary cartridge for particle processing
US9260693B2 (en) 2004-12-03 2016-02-16 Cytonome/St, Llc Actuation of parallel microfluidic arrays
EP1875200A1 (en) * 2005-04-29 2008-01-09 Honeywell International Inc. Cytometer cell counting and size measurement method
JP4995197B2 (en) 2005-07-01 2012-08-08 ハネウェル・インターナショナル・インコーポレーテッド Molding a cartridge having a 3d hydrodynamic focusing
WO2007005974A3 (en) 2005-07-01 2007-06-14 Cleopatra Cabuz A flow metered analyzer
EP1901846B1 (en) 2005-07-01 2015-01-14 Honeywell International Inc. A microfluidic card for rbc analysis
US7843563B2 (en) * 2005-08-16 2010-11-30 Honeywell International Inc. Light scattering and imaging optical system
JP2009508584A (en) * 2005-09-16 2009-03-05 ビージー インプラント インコーポレイテッド Glaucoma treatment apparatus and method
US8068991B2 (en) 2005-11-30 2011-11-29 The Invention Science Fund I, Llc Systems and methods for transmitting pathogen related information and responding
US20080245740A1 (en) * 2007-01-29 2008-10-09 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Fluidic methods
US20090050569A1 (en) * 2007-01-29 2009-02-26 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Fluidic methods
US7384549B2 (en) * 2005-12-29 2008-06-10 Spf Innovations, Llc Method and apparatus for the filtration of biological solutions
US8747669B1 (en) * 2005-12-29 2014-06-10 Spf Innovations, Llc Method and apparatus for the filtration of biological samples
US8617903B2 (en) 2007-01-29 2013-12-31 The Invention Science Fund I, Llc Methods for allergen detection
GB2460196B (en) * 2007-01-29 2011-06-01 Searete Llc Fluidic methods
US20080178692A1 (en) * 2007-01-29 2008-07-31 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Fluidic methods
US20080181821A1 (en) * 2007-01-29 2008-07-31 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Microfluidic chips for allergen detection
US20080179255A1 (en) * 2007-01-29 2008-07-31 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Fluidic devices
US7799656B2 (en) 2007-03-15 2010-09-21 Dalsa Semiconductor Inc. Microchannels for BioMEMS devices
US20090215157A1 (en) * 2007-03-27 2009-08-27 Searete Llc Methods for pathogen detection
US20080241000A1 (en) * 2007-03-27 2008-10-02 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Systems for pathogen detection
US20080241909A1 (en) * 2007-03-27 2008-10-02 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Microfluidic chips for pathogen detection
US20080241935A1 (en) * 2007-03-27 2008-10-02 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Methods for pathogen detection
US20080277332A1 (en) * 2007-05-11 2008-11-13 Becton, Dickinson And Company Micromachined membrane filter device for a glaucoma implant and method for making the same
JP2009083382A (en) * 2007-10-01 2009-04-23 Brother Ind Ltd Image forming device and image processing program
CN102149812A (en) * 2008-02-21 2011-08-10 埃凡特拉生物科技公司 Assays based on liquid flow over arrays
EP2254699A1 (en) * 2008-03-11 2010-12-01 Koninklijke Philips Electronics N.V. Filtering apparatus for filtering a fluid
US20100034704A1 (en) * 2008-08-06 2010-02-11 Honeywell International Inc. Microfluidic cartridge channel with reduced bubble formation
US8037354B2 (en) 2008-09-18 2011-10-11 Honeywell International Inc. Apparatus and method for operating a computing platform without a battery pack
US7927904B2 (en) 2009-01-05 2011-04-19 Dalsa Semiconductor Inc. Method of making BIOMEMS devices
WO2013044109A1 (en) * 2011-09-23 2013-03-28 Siemens Healthcare Diagnostics Inc. Microfluidic device for separating cells from a fluid
EP2587248A1 (en) * 2011-10-25 2013-05-01 Koninklijke Philips Electronics N.V. Filtering particles from blood or other media
EP2748581A1 (en) * 2011-10-25 2014-07-02 Koninklijke Philips N.V. Filtering particles from blood or other media
CN103959037A (en) * 2011-10-25 2014-07-30 皇家飞利浦有限公司 Filtering particles from blood or other media
US8741233B2 (en) 2011-12-27 2014-06-03 Honeywell International Inc. Disposable cartridge for fluid analysis
US8741234B2 (en) 2011-12-27 2014-06-03 Honeywell International Inc. Disposable cartridge for fluid analysis
US8741235B2 (en) 2011-12-27 2014-06-03 Honeywell International Inc. Two step sample loading of a fluid analysis cartridge
US8663583B2 (en) 2011-12-27 2014-03-04 Honeywell International Inc. Disposable cartridge for fluid analysis
US20140323911A1 (en) * 2013-03-15 2014-10-30 Theranos, Inc. Methods and devices for sample collection and sample separation
ES2539843B2 (en) * 2013-11-15 2015-11-16 Universitat Politècnica De Catalunya microfluidic device for separating liquid therefrom liquid containing deformable particles without external energy sources

Citations (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1979001120A1 (en) 1978-05-25 1979-12-27 Department Of Commerce Filtration apparatus for separating blood cell-containing liquid suspensions
EP0231432A2 (en) 1985-12-24 1987-08-12 Kernforschungszentrum Karlsruhe Gmbh Cross-flow microfilter
US4751003A (en) 1985-05-02 1988-06-14 Henkel Kommanditgesellschaft Auf Aktien Crossflow microfiltration process for the separation of biotechnologically produced materials
US4753776A (en) 1986-10-29 1988-06-28 Biotrack, Inc. Blood separation device comprising a filter and a capillary flow pathway exiting the filter
US4801379A (en) 1986-07-23 1989-01-31 Sulzer Brothers Limited Microfilter foil and method of producing same
WO1993022053A1 (en) 1992-05-01 1993-11-11 Trustees Of The University Of Pennsylvania Microfabricated detection structures
US5304487A (en) 1992-05-01 1994-04-19 Trustees Of The University Of Pennsylvania Fluid handling in mesoscale analytical devices
US5338400A (en) 1993-02-25 1994-08-16 Ic Sensors, Inc. Micromachining process for making perfect exterior corner in an etchable substrate
WO1995013860A1 (en) 1993-11-12 1995-05-26 Rijn Cornelis Johannes Maria V Membrane filter and a method of manufacturing the same as well as a membrane
US5498392A (en) 1992-05-01 1996-03-12 Trustees Of The University Of Pennsylvania Mesoscale polynucleotide amplification device and method
WO1996014934A1 (en) 1994-11-14 1996-05-23 Trustees Of The University Of Pennsylvania Mesoscale sample preparation device and systems for determination and processing of analytes
WO1996015576A1 (en) 1994-11-10 1996-05-23 David Sarnoff Research Center, Inc. Liquid distribution system
US5587128A (en) 1992-05-01 1996-12-24 The Trustees Of The University Of Pennsylvania Mesoscale polynucleotide amplification devices
US5726026A (en) 1992-05-01 1998-03-10 Trustees Of The University Of Pennsylvania Mesoscale sample preparation device and systems for determination and processing of analytes

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0414457A (en) * 1990-05-08 1992-01-20 Oki Electric Ind Co Ltd Recording head

Patent Citations (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4212742A (en) 1978-05-25 1980-07-15 United States Of America Filtration apparatus for separating blood cell-containing liquid suspensions
WO1979001120A1 (en) 1978-05-25 1979-12-27 Department Of Commerce Filtration apparatus for separating blood cell-containing liquid suspensions
US4751003A (en) 1985-05-02 1988-06-14 Henkel Kommanditgesellschaft Auf Aktien Crossflow microfiltration process for the separation of biotechnologically produced materials
US4797211A (en) 1985-12-24 1989-01-10 Kernforschungszentrum Karlsruhe Gmbh Cross flow microfilter
EP0231432A2 (en) 1985-12-24 1987-08-12 Kernforschungszentrum Karlsruhe Gmbh Cross-flow microfilter
US4801379A (en) 1986-07-23 1989-01-31 Sulzer Brothers Limited Microfilter foil and method of producing same
US4753776A (en) 1986-10-29 1988-06-28 Biotrack, Inc. Blood separation device comprising a filter and a capillary flow pathway exiting the filter
US5498392A (en) 1992-05-01 1996-03-12 Trustees Of The University Of Pennsylvania Mesoscale polynucleotide amplification device and method
WO1993022053A1 (en) 1992-05-01 1993-11-11 Trustees Of The University Of Pennsylvania Microfabricated detection structures
US5635358A (en) 1992-05-01 1997-06-03 Trustees Of The University Of Pennsylvania Fluid handling methods for use in mesoscale analytical devices
US5587128A (en) 1992-05-01 1996-12-24 The Trustees Of The University Of Pennsylvania Mesoscale polynucleotide amplification devices
US5304487A (en) 1992-05-01 1994-04-19 Trustees Of The University Of Pennsylvania Fluid handling in mesoscale analytical devices
US5726026A (en) 1992-05-01 1998-03-10 Trustees Of The University Of Pennsylvania Mesoscale sample preparation device and systems for determination and processing of analytes
US5338400A (en) 1993-02-25 1994-08-16 Ic Sensors, Inc. Micromachining process for making perfect exterior corner in an etchable substrate
WO1995013860A1 (en) 1993-11-12 1995-05-26 Rijn Cornelis Johannes Maria V Membrane filter and a method of manufacturing the same as well as a membrane
WO1996015576A1 (en) 1994-11-10 1996-05-23 David Sarnoff Research Center, Inc. Liquid distribution system
WO1996014934A1 (en) 1994-11-14 1996-05-23 Trustees Of The University Of Pennsylvania Mesoscale sample preparation device and systems for determination and processing of analytes

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
Gravesen, P., et al. (1993), "Microfluidics-a review," J. Micromech. Microeng. 3:168-182.
Gravesen, P., et al. (1993), "Microfluidics—a review," J. Micromech. Microeng. 3:168-182.
Kittisland G., and Stemme, G. (1990), "A Sub-micron Particle Filter in Silicon," Sensors and Actuators, A21-A23:904-907.
Reisman, A., et al. (1979), "The Controlled Etching of Silicon in Catalyzed Ethylenediamine-Pyrocatechol-Water Solutions," J. Electrochem. Soc. 126:1406-1415.
Shoji, S. and Esashi, M. (1994) "Microflow devices and system," J. Micromechanics and Microengineering 4:157-171.
Stemme, G. and Kittisland, G. (1988), "New fluid filter structure in silicon fabricated using a self-aligning technique,"Appl. Phys. Lett. 53:1566-1568.
Wallis, G. and Pomerantz, D.I (1969) J. Appl. Physics 40:3946-3949.
Wilding, P., et al., (1994), "Manipulation and Flow of Biological Fluids in Straight Channels Micromachined in Silicon," Clin. Chem. 40:43-47.

Cited By (75)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
USRE41762E1 (en) 2001-02-14 2010-09-28 Stc.Unm Nanostructured separation and analysis devices for biological membranes
USRE42315E1 (en) 2001-02-14 2011-05-03 Stc.Unm Nanostructured separation and analysis devices for biological membranes
USRE42249E1 (en) 2001-02-14 2011-03-29 Stc.Unm Nanostructured separation and analysis devices for biological membranes
US20020185431A1 (en) * 2001-06-07 2002-12-12 Nanostream, Inc. Microfluidic filter
US6811695B2 (en) 2001-06-07 2004-11-02 Nanostream, Inc. Microfluidic filter
US20040256318A1 (en) * 2001-10-26 2004-12-23 Kazuhiro Iida Separating device, analysis system separation method and method of manufacture of separating device
US7318902B2 (en) 2002-02-04 2008-01-15 Colorado School Of Mines Laminar flow-based separations of colloidal and cellular particles
US20080093306A1 (en) * 2002-02-04 2008-04-24 Colorado School Of Mines Cell sorting device and method of manufacturing the same
US20090188795A1 (en) * 2002-02-04 2009-07-30 Colorado School Of Mines Cell sorting device and method of manufacturing the same
US7472794B2 (en) 2002-02-04 2009-01-06 Colorado School Of Mines Cell sorting device and method of manufacturing the same
US7276170B2 (en) 2002-02-04 2007-10-02 Colorado School Of Mines Laminar flow-based separations of colloidal and cellular particles
US20060169642A1 (en) * 2002-02-04 2006-08-03 John Oakey Laminar flow-based separations of colloidal and cellular particles
US20030159999A1 (en) * 2002-02-04 2003-08-28 John Oakey Laminar Flow-Based Separations of Colloidal and Cellular Particles
US20070131622A1 (en) * 2002-02-04 2007-06-14 Colorado School Of Mines Cell sorting device and method of manufacturing the same
US6925392B2 (en) 2002-08-21 2005-08-02 Shell Oil Company Method for measuring fluid chemistry in drilling and production operations
US7743928B2 (en) 2002-09-07 2010-06-29 Timothy Crowley Integrated apparatus and methods for treating liquids
US20040129678A1 (en) * 2002-09-07 2004-07-08 Timothy Crowley Integrated apparatus and methods for treating liquids
US20060134599A1 (en) * 2002-09-27 2006-06-22 Mehmet Toner Microfluidic device for cell separation and uses thereof
US8372579B2 (en) 2002-09-27 2013-02-12 The General Hospital Corporation Microfluidic device for cell separation and uses thereof
US8895298B2 (en) 2002-09-27 2014-11-25 The General Hospital Corporation Microfluidic device for cell separation and uses thereof
US8304230B2 (en) 2002-09-27 2012-11-06 The General Hospital Corporation Microfluidic device for cell separation and uses thereof
US8986966B2 (en) 2002-09-27 2015-03-24 The General Hospital Corporation Microfluidic device for cell separation and uses thereof
US20040195099A1 (en) * 2003-04-04 2004-10-07 Jacobson Stephen C. Sample filtration, concentration and separation on microfluidic devices
US7648835B2 (en) 2003-06-06 2010-01-19 Micronics, Inc. System and method for heating, cooling and heat cycling on microfluidic device
US7544506B2 (en) 2003-06-06 2009-06-09 Micronics, Inc. System and method for heating, cooling and heat cycling on microfluidic device
US20050129582A1 (en) * 2003-06-06 2005-06-16 Micronics, Inc. System and method for heating, cooling and heat cycling on microfluidic device
US20090081771A1 (en) * 2003-06-06 2009-03-26 Micronics, Inc. System and method for heating, cooling and heat cycling on microfluidic device
WO2004113877A1 (en) * 2003-06-13 2004-12-29 The General Hospital Corporation Microfluidic systems for size based removal of red blood cells and platelets from blood
US20050266433A1 (en) * 2004-03-03 2005-12-01 Ravi Kapur Magnetic device for isolation of cells and biomolecules in a microfluidic environment
WO2005095954A1 (en) * 2004-03-31 2005-10-13 All Medicus Co., Ltd. A filter for separating blood-corpuscles and plasma from blood, and blood analysis system using this filter
US20060171846A1 (en) * 2005-01-10 2006-08-03 Marr David W M Microfluidic systems incorporating integrated optical waveguides
WO2006079007A3 (en) * 2005-01-21 2006-11-16 Harvard College Microconcentrator/microfilter
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US20090101559A1 (en) * 2005-01-21 2009-04-23 Anand Bala Subramaniam Microconcentrator/Microfilter
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US8585971B2 (en) 2005-04-05 2013-11-19 The General Hospital Corporation Devices and method for enrichment and alteration of cells and other particles
US8021614B2 (en) 2005-04-05 2011-09-20 The General Hospital Corporation Devices and methods for enrichment and alteration of cells and other particles
US9174222B2 (en) 2005-04-05 2015-11-03 The General Hospital Corporation Devices and method for enrichment and alteration of cells and other particles
US8921102B2 (en) 2005-07-29 2014-12-30 Gpb Scientific, Llc Devices and methods for enrichment and alteration of circulating tumor cells and other particles
US20070059718A1 (en) * 2005-09-15 2007-03-15 Mehmet Toner Systems and methods for enrichment of analytes
US20070059683A1 (en) * 2005-09-15 2007-03-15 Tom Barber Veterinary diagnostic system
US20090148847A1 (en) * 2006-03-15 2009-06-11 Micronics, Inc. Rapid magnetic flow assays
US8222023B2 (en) 2006-03-15 2012-07-17 Micronics, Inc. Integrated nucleic acid assays
US8772017B2 (en) 2006-03-15 2014-07-08 Micronics, Inc. Integrated nucleic acid assays
US20070289917A1 (en) * 2006-06-15 2007-12-20 Mylin John M Separation system and method of operating
US20080007838A1 (en) * 2006-07-07 2008-01-10 Omnitech Partners, Inc. Field-of-view indicator, and optical system and associated method employing the same
US20090325276A1 (en) * 2006-09-27 2009-12-31 Micronics, Inc. Integrated microfluidic assay devices and methods
US20090026387A1 (en) * 2007-07-03 2009-01-29 Colorado School Of Mines Optical-based cell deformability
US8119976B2 (en) 2007-07-03 2012-02-21 Colorado School Of Mines Optical-based cell deformability
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US20090110010A1 (en) * 2007-09-26 2009-04-30 Colorado School Of Mines Fiber-focused diode-bar optical trapping for microfluidic manipulation
US9132398B2 (en) 2007-10-12 2015-09-15 Rheonix, Inc. Integrated microfluidic device and methods
US20100021910A1 (en) * 2008-07-18 2010-01-28 Canon U.S. Life Sciences, Inc. Methods and Systems for Microfluidic DNA Sample Preparation
US9513196B2 (en) 2008-07-18 2016-12-06 Canon U.S. Life Sciences, Inc. Methods and systems for microfluidic DNA sample preparation
US8313906B2 (en) 2008-07-18 2012-11-20 Canon U.S. Life Sciences, Inc. Methods and systems for microfluidic DNA sample preparation
US20100230334A1 (en) * 2009-03-12 2010-09-16 Samsung Electronics Co., Ltd. Filter unit for separating target material and microfluidic device including the filter unit
US20110014605A1 (en) * 2009-07-17 2011-01-20 Canon U.S. Life Sciences, Inc. Methods and systems for dna isolation on a microfluidic device
US9116088B2 (en) 2009-07-17 2015-08-25 Canon U.S. Life Sciences, Inc. Methods and systems for DNA isolation on a microfluidic device
US8304185B2 (en) 2009-07-17 2012-11-06 Canon U.S. Life Sciences, Inc. Methods and systems for DNA isolation on a microfluidic device
WO2012094170A2 (en) * 2011-01-03 2012-07-12 The Regents Of The University Of California Methods and microfluidic devices for concentrating and transporting particles
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US9487812B2 (en) 2012-02-17 2016-11-08 Colorado School Of Mines Optical alignment deformation spectroscopy
US20130264295A1 (en) * 2012-04-05 2013-10-10 Samsung Electronics Co., Ltd. Filter for capturing target material
US9081001B2 (en) 2012-05-15 2015-07-14 Wellstat Diagnostics, Llc Diagnostic systems and instruments
US9075042B2 (en) 2012-05-15 2015-07-07 Wellstat Diagnostics, Llc Diagnostic systems and cartridges
US9625465B2 (en) 2012-05-15 2017-04-18 Defined Diagnostics, Llc Clinical diagnostic systems
US9213043B2 (en) 2012-05-15 2015-12-15 Wellstat Diagnostics, Llc Clinical diagnostic system including instrument and cartridge
WO2014138715A1 (en) * 2013-03-08 2014-09-12 Duke University Devices, systems, and methods for acoustically -enhanced magnetophoresis
US9410663B2 (en) 2013-03-15 2016-08-09 Genmark Diagnostics, Inc. Apparatus and methods for manipulating deformable fluid vessels
US9453613B2 (en) 2013-03-15 2016-09-27 Genmark Diagnostics, Inc. Apparatus, devices, and methods for manipulating deformable fluid vessels
US9222623B2 (en) 2013-03-15 2015-12-29 Genmark Diagnostics, Inc. Devices and methods for manipulating deformable fluid vessels
US9498778B2 (en) 2014-11-11 2016-11-22 Genmark Diagnostics, Inc. Instrument for processing cartridge for performing assays in a closed sample preparation and reaction system
US9598722B2 (en) 2014-11-11 2017-03-21 Genmark Diagnostics, Inc. Cartridge for performing assays in a closed sample preparation and reaction system

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